Colorectal cancer (CRC) is the third most commonly diagnosed and leading cause of death worldwide. On the other hand, glioblastoma multiforme (GBM) is the most prevalent and aggressive primary malignant brain tumor in adults. Inherited diseases of DNA mismatch repair (MMR) can cause multiple cancers in the same patient including CRC and GBM. In this study, we report a 59-year-old woman presented with fatigue, constipation, abdominal distention, perianal pain, right-sided arm weakness, and personality changes. After investigations, it was diagnosed that sporadic metastatic CRC and GBM occurred simultaneously in the same patient, which was confirmed by colonoscopy, biopsy, imaging, and molecular testing. As the treatment of two cancers in the same patient is unique and complex, the absence of guidelines for such cases was discussed in a multidisciplinary tumor board including surgeons, medical, and radiation oncologists.